Claims for Patent: 8,092,803

Summary for Patent: 8,092,803

Title:	VEGF antagonist formulations for intravitreal administration
Abstract:	Ophthalmic formulations of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist are provided suitable for intravitreal administration to the eye. The ophthalmic formulations include a stable liquid formulation and a lyophilizable formulation. Preferably, the protein antagonist has the amino acid sequence shown in SEQ ID NO:4.
Inventor(s):	Furfine; Eric (Concord, MA), Dix; Daniel (LaGrangeville, NY), Graham; Kenneth S. (Pleasant Valley, NY), Frye; Kelly (Pomona, NY)
Assignee:	Regeneron Pharmaceuticals, Inc. (Tarrytown, NY)
Application Number:	12/833,417
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,092,803
Patent Claims:	1. A stable liquid ophthalmic formulation of a vascular endothelial growth factor (VEGF) antagonist, comprising: (a) between 50 mg/ml to about 10 mg/ml of a VEGF antagonist comprising amino acids 27-475 of SEQ ID NO:4; (b) about 0.03% to about 0.1% polysorbate; (c) about 5-40 mM of sodium phosphate buffer, pH of about 5.8 to about 7.0; and (d) either: (i) about 5% sucrose and about 40 to about 50 mM NaCl, or (ii) about 135 mM NaCl, wherein at least 99% of the VEGF antagonist is present in native conformation following storage at 5.degree. C. for 2 months as measured by size exclusion chromatography. 2. The formulation of claim 1, comprising between 50 mg/ml to about 10 mg/ml of the VEGF antagonist, about 10 mM sodium phosphate buffer, about 40 mM NaCl, about 0.03% polysorbate, and about 5% sucrose, pH about 6.2-6.3. 3. The formulation of claim 2, comprising about 10 to about 40 mg/ml of the VEGF antagonist. 4. The formulation of claim 3, comprising VEGF antagonist at a concentration of about 10 mg/ml. 5. The formulation of claim 3, comprising VEGF antagonist at a concentration of about 40 mg/ml. 6. The formulation of claim 1, comprising between 50 mg/ml to about 10 mg/ml of the VEGF antagonist, about 10 mM sodium phosphate buffer, about 135 mM NaCl and about 0.03% polysorbate, pH about 6.2-6.3. 7. The formulation of claim 6, comprising about 10 to about 40 mg/ml of the VEGF antagonist. 8. The formulation of claim 7, comprising VEGF antagonist at a concentration of about 10 mg/ml. 9. The formulation of claim 7, comprising VEGF antagonist at a concentration of about 40 mg/ml. 10. A pre-filled syringe suitable for intravitreal administration comprising the formulation of claim 1. 11. A pre-filled syringe suitable for intravitreal administration comprising the formulation of claim 4. 12. A pre-filled syringe suitable for intravitreal administration comprising the formulation of claim 5. 13. A pre-filled syringe suitable for intravitreal administration comprising the formulation of claim 6. 14. A pre-filled syringe suitable for intravitreal administration comprising the formulation of claim 8. 15. A pre-filled syringe suitable for intravitreal administration comprising the formulation of claim 9. 16. A non-liquid formulation of a vascular endothelial growth factor (VEGF) antagonist made according to the steps of: (a) combining in a liquid solution the following excipients: (i) about 5-50 mg/ml of the VEGF antagonist, comprising amino acids 27-475 of SEQ ID NO:4; (ii) about 5-25 mM of sodium phosphate buffer, pH about 5.8-7.0; (iii) about 0.01-0.15% of an organic co-solvent, selected from the group consisting of polysorbate, polyethylene glycol (PEG), propylene glycol, and a combination thereof; and (iv) about 1-10% of a stabilizing agent selected from the group consisting of sucrose, sorbitol, glycerol, trehalose, and mannitol; and (b) lyophilizing the combination of step (a), wherein at least about 99% of the VEGF antagonist is present in native conformation as measured by size exclusion chromatography following storage at 5.degree. C. for 2 months. 17. The non-liquid formulation of claim 16, wherein about 20 mg/ml of the VEGF antagonist, about 5 mM sodium phosphate buffer, about 0.015% polysorbate, about 2.5% sucrose, and about 20 mM sodium chloride, pH about 6.2-6.3 are combined at step (a). 18. The non-liquid formulation of claim 16, wherein about 20 mg/ml of the VEGF antagonist, about 5 mM sodium phosphate buffer, about 0.015% polysorbate, and about 67.5 mM sodium chloride, pH about 6.2-6.3 are combined at step (a). 19. The non-liquid formulation of claim 16, wherein the formulation can be reconstituted in about 0.7 minutes or less.

Details for Patent 8,092,803

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Regeneron Pharmaceuticals, Inc.	EYLEA	aflibercept	Injection	125387	11/18/2011		2039-02-26
Regeneron Pharmaceuticals, Inc.	EYLEA	aflibercept	Injection	125387	08/16/2018		2039-02-26

International Patent Family for US Patent 8,092,803

Country	Patent Number	Estimated Expiration
Australia	2007261536
Brazil	PI0713749
Canada	2654510
China	101478949
China	104434770
Cyprus	1114244